NEUROCHEMICAL CONTROL OF OXYTOCIN RELEASE

当哺乳期大鼠注射多巴胺（DA）激动剂时， 产后2-5天服用溴隐亭， 在不取消泌乳的情况下， 后代表现出结节漏斗DA（TIDA）活性降低 系统和血清PRL升高。此外，在成年人中， 新生儿PRL缺乏的脑垂体细胞 大鼠，它们的催乳细胞显示出对 DA的PRL抑制作用和对PRL的反应性增加- DA的抑制作用和对PRL的反应性增加- TRH的刺激作用。这些影响（1）不是由于非特异性 溴隐亭的影响，因为基本上检测不到的水平， 药物通过乳汁从母亲传给新生儿; 2）预防 通过替代溴隐亭治疗的母亲的PRL;和3）不 如果在第二次怀孕期间向母亲施用溴隐亭， 产后一周这些发现表明， 新生儿PRL影响TIDA的生长和/或成熟 神经元以及垂体催乳素，以及缺乏牛奶- 在出生后的关键时期， PRL分泌的神经内分泌调节的后果。具体 本建议的目的是：1）建立正常的时间进程 为了TIDA系统的功能开发，使用以下测量结果： DA浓度和合成速率，并检测PRL和 新生儿PRL缺乏症的发展过程中：2） 探讨新生儿PRL缺乏对TIDA数量的影响 神经元，使用酪氨酸羟化酶的免疫细胞化学; 30至 检查新生儿PRL缺乏是否会改变TIDA的反应 神经元的正常调节的影响，使用iv体内和体外 探讨新生儿PRL缺乏的后果 在成人调节PRL的合成和释放的刺激或 抑制性促垂体激素，或雌二醇，使用培养的 垂体前叶细胞; 5）测试是否受体结合 促垂体激素和/或它们与第二信使的偶联 系统，如腺苷酸环化酶/cAMP， 新生儿PRL缺乏症; 6）检测新生儿是否PRL缺乏症 影响垂体催乳细胞的数量和/或形态， PRL的分泌形式，以及PRL分泌的特点， 在大鼠的整个生命周期中，

When lactating rats are injected with the dopamine (DA) agonist bromocriptine during days 2-5 postpartum, which substantially decreases the concentrations of PRL in milk without abolishing lactation, their offspring exhibit decreased activity of the tuberoinfundibular DA (TIDA) system and elevated serum PRL as young adults. In addition, in the adult, there are more cells in the pituitary glands from neonatal PRL-deficient rats, and their lactotrophe cells show decreased responsiveness to the PRL-inhibiting effects of DA and increased responsiveness to the PRL- inhibiting effects of DA and increased responsiveness to the PRL- stimulating effects of TRH. These effects 1) are not due to non-specific effects of bromocriptine since essentially undetectable levels of the drug pass from the mother to the neonate via the milk; 2) are prevented by the replacement of PRL to bromocriptine-treated mothers; and 3) do not occur if bromocriptine is administered to the mothers during the second postnatal week. These findings suggest the hypothesis that milk- derived PRL in the neonate influences the growth and/or maturation of TIDA neurons as well as pituitary lactotrophes, and that a deficiency in milk- derived PRL during a critical postnatal period may have long-lasting consequences for neuroendocrine regulation of PRL secretion. The specific aims of the present proposal are: 1) to establish the normal time course for the functional development of the TIDA system, using measurements of DA concentration and synthesis rate, and to test the effects of PRL and of neonatal PRL deficiency on the course of this development: 2) to investigate the effects of neonatal PRL deficiency on the numbers of TIDA neurons, using immunocytochemistry for tyrosine hydroxylase; 30 to examine whether neonatal PRL deficiency alters the response of TIDA neurons to their normal regulatory influences, using iv vivo and in vitro approaches; 4) to investigate the consequences of neonatal PRL deficiency on the adult regulation of PRL synthesis and release by stimulatory or inhibitory hypophyseotropic hormones, or by estradiol, using cultured anterior pituitary cells; 5) to test whether the receptor binding of hypophyseotropic hormones and/or their coupling to a second messenger system, such as adenylate cyclase/cAMP, are permanently altered by neonatal PRL deficiency; 6) to test whether neonatal PRL deficiency affects the numbers and/or morphology of pituitary lactotrophe cells, the secretory forms of PRL, and the characteristics of PRL secretion from lactotrophe cells over the lifespan of the rat.